Multi-slice spatial transcriptome domain analysis with SpaDo

With the rapid advancements in spatial transcriptome sequencing, multiple tissue slices are now available, enabling the integration and interpretation of spatial cellular landscapes. Herein, we introduce SpaDo, a tool for multi-slice spatial domain analysis, including modules for multi-slice spatial domain detection, reference-based annotation, and multiple slice clustering at both single-cell and spot resolutions. We demonstrate SpaDo’s effectiveness with over 40 multi-slice spatial transcriptome datasets from 7 sequencing platforms. Our findings highlight SpaDo’s potential to reveal novel biological insights in multi-slice spatial transcriptomes. Supplementary Information The online version contains supplementary material available at 10.1186/s13059-024-03213-x.


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Spatial domain annotation.

Fig. S1
Fig. S1 SpaDo detectes spatial domain with a multi-resolution schema hieratically.a Manually annotated layer structure of DLPFC_151673 dataset.b The UMAP visualization of SPACE and the corresponding hierarchical clustering result.c Location of spatial domains detected by SpaDo.d Location of the multi-resolution spatial domains detected by SpaDo.

Fig. S2
Fig. S2 The multi-resolution spatial domain detection results of osmFISH data.

Fig. S4 .
Fig. S4.Details of benchmark in osmFISH data related to Fig. 2a. a Layer structure and cell type of osmFISH data from the original paper.b ARI and visualization of domain detection for each method.The regions in the red rectangular are examples showing the difference of detected spatial domains by SpaDo and other methods.

Fig. S5
Fig. S5 Details of benchmark in seqFISH+ data related to Fig. 2a. a Brain regions and cell types of seqFISH+ data from the original paper.b ARI and visualization of domain detection for each method.

Fig. S6
Fig. S6 Details of benchmark in STARmap data related to Fig. 2a. a Brain regions and cell types of STARmap data from the original paper.b ARI and visualization of domain detection for each method.The regions in the red rectangular are examples showing the difference of detected spatial domains by SpaDo and other methods.

Fig. S7
Fig. S7 Performance of SpaDo can be further improved by integrating multiple slices.a Manually annotated labels of layers for DLPFC_151675 and DLPFC_151676 datasets.b Location and ARI of SpaDo for single slice.c Location and ARI of SpaDo by integrating DLPFC_151675 and DLPFC_151676 dataset.

Fig. S8
Fig. S8 Benchmarking TLS-like domain detection when domain number is set to 10 related to Fig. 2e.

Fig. S10
Fig. S10 SpaDo enables cross-slice spatial domain detection when spatial domain number is set to 3. a Cell type proportion of each detected spatial domain.b Proportion of detected spatial domains for each RCC slice.c Umap and hierarchical clustering result of SPACE on 5 RCC slices.d Location of detected spatial domains against true TLS labels in all 5 RCC slices.

Fig. S11
Fig. S11 The clustering results of SpaDo with different domain number in human heart dataset related to Fig. 7f.

Fig. S12
Fig. S12 SpaDo enables slice-level clustering analysis in chicken heart dataset.a Umap and hierarchical clustering result of SPACE on 12 chicken heart slices.(Colored by detected spatial domains).b Umap of SPACE on 12 chicken heart slices.(Colored by slices).c Cell type proportion of each detected domain.d Location of each detected domain in 12 slices.e Heatmap of clustering results of 12 slices using average cell type proportion as baseline.f Heatmap of clustering results of 12 slices using domain composition detected by SpaDo.

Fig. S13
Fig. S13 The clustering results of SpaDo with different domain number in chicken heart dataset related to Fig. S12.

Fig. S14
Fig. S14 SpaDo enables slice-level clustering analysis in human cortical organoid dataset.a Location of each detected domain on 10 cortical organoid slices.b Cell type proportion of each detected domain.c Heatmap of clustering results of 10 cortical organoid slices using average cell type proportion as baseline.d Heatmap of clustering results of 10 cortical organoid slices using domain composition detected by SpaDo.e Clustering results of SpaDo with different domain number (domain number is set to 7).f Clustering results of SpaDo with different domain number (domain number is set to 11).